Increased calcium triggers several different responses in nerve cells including long term changes that are thought to be mediated through alterations in gene expression. These experiments seek to investigate the mechanism whereby calcium increases expression of the immediate early gene c-fos. Previous research by the applicant has led to the model that a calcium-calmodulin complex activates a calcium-regulated kinase that activates CREB at serine- 133. This may then lead to the binding of CBP to the phosphorylated CREB, which then promotes activation of c-fos. The applicant intends to continue investigating this activation by 1) identifying proposed factors that bind to CREB to form heterodimers; 2) characterizing a second event needed for CREB- mediated transcriptional activation; and 3) identifying the kinase responsible for CREB phosphorylation.